The Anti-Fungal drug Griseofulvin: Like Chemotheraphy but Without its Side Effects

Cellular division:

Mitosis is a part of the cell life cycle in which the division of the nucleus takes place so that finally one cell will become two cells. This is the process in which chromosomes in a cell nucleus are separated into two identical sets of chromosomes, and each set ends up in its own nucleus. The result is two genetically identical daughter nuclei.

Just as our bodies rely on bones for structural support, our cells rely on a cellular skeleton. That is the cytoskeleton which not only helps cells keep their shape but also transports material within cells and coordinates cell division. Thus, during the cell division, the separation of the chromosomes is supported and facilitated by a network of microtubules (component of the cytoskeleton) that transport and align the two chromosomes to opposite sides, at the cell equator.

Microtubules are small tubes, located within the cell’s cytoplasm, with a diameter of about 10-20nm and with their ends designated the (−) and (+) ends. When needed, microtubules can elongate fast, significantly more rapid at the (+) end. The building blocks of microtubule are called α- and β-tubulin. When microtubules elongate at the (+) end, it means that β-subunits are binding while at the (−) end α-subunits are binding.

During mitosis, centrosomes function as spindle poles, directing the formation of bipolar spindles, a process essential for accurate chromosomal separation. Centrosomes duplicate precisely once per cell cycle to assure spindle bipolarity, with each daughter cell receiving one centrosome.

In a few words, during mitosis a cell splits its nucleus in two. One part is going one way and the other part goes the opposite direction organised by centrosome and supported by microtubule “arms” with their motors (all under the name of mitotic spindles).

However, in cancer this division leads not only to two separations but to multiple such separations. Such error would immediately trigger cell death in a normal cell. However, cancer cells can overcome this problem by having a mechanism to cluster the centrosomes in to two opposite groups (spindle poles) of multiple centrosomes enabling bipolar cell division.

Recent screenings of various drugs have indicated that Griseofulvin, an antifungal FDA approved drug used for fungal nail infections, cheap and available at the pharmacies, induces spindle multipolarity (Ref.). As we discussed above, for cell division bipolarity is required and not multipolarity. Thus, multipolarity induced by Griseofulvin, leads to mitotic arrest, and subsequent cell death in multiple tumor cell lines. This multipolarity induced by Griseofulvin is due to an induction of spindle tension by interaction with and suppression of microtubule dynamics.

As a result, Griseofulvin inhibits microtubule dynamics, which leads to spindle tension, which leads to centrosome declustering in cells with more than two centrosomes, leading to multipolar cell division and ultimately cell death.

Due to its mechanism of action, Griseofulvin behaves in a similar way as chemotheraphies of the Tubulin Interactive agents type, that act by binding to specific sites on tubulin, the building blocks of cellular microtubules. When these agents bind on the protein, the cell can not form microtubules. Tubulin interactive agents include Vincristine, Vinblasune, and Paclitaxel. Griseofulvin shares its binding site in tubulin with paclitaxel and kinetically suppresses microtubule dynamics in a similar manner (Ref.).

Interestingly, it has been suggested that Griseofulvin may be more powerful than Paclitaxel: “Based on our data, RedBr-Nos and Griseofulvin showed more dramatic effects on centrosome declustering and inhibition of neurite formation as compared with PJ-34 and Paclitaxel. In sum, our findings reveal the previously underappreciated aspects of the actions of centrosome-declustering drugs, their potential application as anti-metastatics and the importance of interphase as a chemotherapeutic target.” (Ref.)

As a side note, Griseofulvin (as well as other microtubule modulators) may also inhibit steroidogenesis (Ref.). This is probably the case in normal adrenal cells since in adrenal cancer cells it seems that Griseofulvin actually leads to an increase of the steroid hormone production such as cortisole, possibly due to adrenal cancer cell apoptosis and release of that, but the mechanism remains still unclear (Ref.).

In view of its ability to stabilize microtubule dynamics and to inhibit microtubule polymerization in human cells, it is remarkable that griseofulvin is well-tolerated when given to humans for the treatment of fungal infections (Ref.) Possibly, the lack of toxicity to normal cells is related to the fact that unlike vincas and taxanes, which inhibit cancer cell proliferation in nanomolar concentration range, Griseofulvin acts in micromolar range. So, the working latitude of Griseofulvin is larger. The lack of significant toxicity of griseofulvin in humans makes this drug relevant as a centrosomal cluster inhibitor.

Due to its mechanism of action, Griseofulvin is relevant for most type of cancers, possibly even more for those fast developing, alone or in combination with other therapies.

Note that a few other drugs that I intend to discuss in other posts, an anti tusive (Noscapine) and an anti worm (Mebendazole) drugs, have similar mode of action as Griseofulvin and consequently are very relevant as potential anti cancer drugs.

Finally, I would like to mention that while Griseofulvin potential as a microtubule dynamics inhibitor is know for long time, one of the first paper highlighting its potential in cancer was published by the German Cancer Research Center from Heidelberg, in 2007 (Ref.). (This to me is a stamp of high quality work. Also note that this is the same center that for the first time applied and demonstrated for the first time the potential of anti cancer effects of Salinomycin in humans.) Following this publication, a website was build to try create awareness about the potential of Griseofulvin in cancer and possibly collect data from patients using it. Here is the link to the website: http://moderatorgriseofulvin.beepworld.de I suspect this was build by a scientist involved in the German research, who intended to share with the world these relevant findings. However, it seems this website never really reached those potentially interested but hopefully that will change in the future.

In conclusion, here we have a drug that acts as some of the chemotheraphies in the market, but in contrast to those Griseofulvin has a good safety profile and is available to all at very low cost.

In general, all human malignancies are potential targets for centrosomal cluster inhibitors since almost all malignant neoplasias examined to date harbour centrosome aberrations.

Griseofulvin as an anti cancer treatment has been patented already in 1997, by The Procter & Gamble Company (Ref.). After the German Cancer Research Center from Heidelberg confirmed its anti cancer potential and understood the mechanism behind, another patent has been filed by the same organization, focused on improving anti cancer activity and bio-availability (Ref.).

Administartion and dose:

Griseofulvin comes as a tablet, capsule, and liquid to take by mouth.

About two years ago I discussed with doctors at German hospitals administrating this drug to cancer patients with good results. They were administrating to patients at a dose of 1.5g/day (500mg 3x/day). Some patients were taking it daily for several years.

Safety and Toxicity:

This dose is higher than the 500mg to 1000mg that is recommended. Therefore, the doctors were following the liver function of patients taking the drug. However, no specific issue has been reported.

A pharmaceutical composition for the treatment of cancers or tumors in mammals is disclosed which comprises griseofulvin. A chemotherapeutic agent can be used in conjunction with griseofulvin as can potentiators. Griseofulvin can also be used to treat viral infections, either alone, in conjunction with other viral agents or with a potentiator.

Together with a recent report indicating that griseofulvin, either alone or in combination with nocodazole, inhibits tumor formation in nude mice (47), and in view of its lack of significant toxicity in humans, the data presented here supports the notion that griseofulvin might be useful for the treatment of cancer

Supernumerary centrosomes and aneuploidy are associated with a malignant phenotype of tumor cells. Centrosomal clustering is a mechanism used by cancer cells with supernumerary centrosomes to solve the threatening problem of multipolar spindles. Griseofulvin is an antifungal substance that interferes with the microtubule apparatus and inhibits centrosomal clustering. It has also been demonstrated that griseofulvin inhibits the growth of tumor cells in vitro and in vivo. However, it is not yet known whether treatment with griseofulvin inhibits growth of adrenocortical tumor cells. We studied the viability and antiproliferative effects of griseofulvin on cultured NCI-H295R adrenocortical carcinoma cells using Wst-1-, BrdUrd-, and [³H]-thymidine assays. For the detection of apoptosis we used a caspase 3/7 cleavage assay and light microscopy techniques. We observed that incubation with griseofulvin for 24-48 h leads to a decrease in the viability and proliferation of NCI-H295R cells in a dose-dependent manner. Significant effects could be observed after incubation with griseofulvin as measured by Wst-1-, BrdUrd-, and [³H]dT- uptake assays. Apoptosis of NCI-H295R cells was increased in a dose-dependent manner up to 4.5-fold after incubation with griseofulvin 40 μM for 24 h as shown by caspase 3/7 cleavage assay and light microscopy. With regard to new treatment strategies for adrenocortical cancer, griseofulvin, and possibly other agents, which interfere with the microtubule apparatus and inhibit centrosomal clustering, may turn out to be interesting targets for further research.

Nearly a century ago, cell biologists postulated that the chromosomal aberrations blighting cancer cells might be caused by a mysterious organelle-the centrosome-that had only just been discovered. For years, however, this enigmatic structure was neglected in oncologic investigations and has only recently reemerged as a key suspect in tumorigenesis. A majority of cancer cells, unlike healthy cells, possess an amplified centrosome complement, which they manage to coalesce neatly at two spindle poles during mitosis. This clustering mechanism permits the cell to form a pseudo-bipolar mitotic spindle for segregation of sister chromatids. On rare occasions this mechanism fails, resulting in declustered centrosomes and the assembly of a multipolar spindle. Spindle multipolarity consigns the cell to an almost certain fate of mitotic arrest or death. The catastrophic nature of multipolarity has attracted efforts to develop drugs that can induce declustering in cancer cells. Such chemotherapeutics would theoretically spare healthy cells, whose normal centrosome complement should preclude multipolar spindle formation. In search of the ‘Holy Grail’ of nontoxic, cancer cell-selective, and superiorly efficacious chemotherapy, research is underway to elucidate the underpinnings of centrosome clustering mechanisms. Here, we detail the progress made towards that end, highlighting seminal work and suggesting directions for future research, aimed at demystifying this riddling cellular tactic and exploiting it for chemotherapeutic purposes. We also propose a model to highlight the integral role of microtubule dynamicity and the delicate balance of forces on which cancer cells rely for effective centrosome clustering. Finally, we provide insights regarding how perturbation of this balance may pave an inroad for inducing lethal centrosome dispersal and death selectively in cancer cells.

The complicity of centrosomes in carcinogenesis is unmistakable. Mounting evidence clearly implicates a robust correlation between centrosome amplification (CA) and malignant transformation in diverse tissue types. Furthermore, CA has been suggested as a marker of cancer aggressiveness, in particular the invasive phenotype, in breast and prostate cancers. One means by which CA promotes malignancy is through induction of transient spindle multipolarity during mitosis, which predisposes the cell to karyotypic changes arising from low-grade chromosome mis-segregation. It is well recognized that during cell migration in interphase, centrosome-mediated nucleation of a radial microtubule array is crucial for establishing a polarized Golgi apparatus, without which directionality is precluded. The question of how cancer cells maneuver their supernumerary centrosomes to achieve directionality during cell migration is virtually uncharted territory. Given that CA is a hallmark of cancers and has been correlated with cancer aggressiveness, malignant cells are presumably competent in managing their centrosome surfeit during directional migration, although the cellular logistics of this process remain unexplored. Another key angle worth pondering is whether an overabundance of centrosomes confers some advantage on cancer cells in terms of their migratory and invasive capabilities. Recent studies have uncovered a remarkable strategy that cancer cells employ to deal with the problem of excess centrosomes and ensure bipolar mitoses, viz., centrosome clustering. This review aims to change the narrative by exploring how an increased centrosome complement may, via aneuploidy-independent modulation of the microtubule cytoskeleton, enhance directional migration and invasion of malignant cells. We postulate that CA imbues cancer cells with cytoskeletal advantages that enhance cell polarization, Golgi-dependent vesicular trafficking, stromal invasion, and other aspects of metastatic progression. We also propose that centrosome declustering may represent a novel, cancer cell-specific antimetastatic strategy, as cancer cells may rely on centrosome clustering during migration as they do in mitosis. Elucidation of these details offers an exciting avenue for future research, as does investigating how CA may promote metastasis through enhanced directional migration.

Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These “biological vectors” can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.

Background: Griseofulvin, an antifungal drug, has recently been shown to inhibit proliferation of various types of cancer cells and to inhibit tumor growth in athymic mice. Due to its low toxicity, griseofulvin has drawn considerable attention for its potential use in cancer chemotherapy. This work aims to understand how griseofulvin suppresses microtubule dynamics in living cells and sought to elucidate the antimitotic and antiproliferative action of the drug.

Methods: The effects of griseofulvin on the dynamics of individual microtubules in live MCF-7 cells were measured by confocal microscopy. Immunofluorescence microscopy, western blotting and flow cytometry were used to analyze the effects of griseofulvin on spindle microtubule organization, cell cycle progression and apoptosis. Further, interactions of purified tubulin with griseofulvin were studied in vitro by spectrophotometry and spectrofluorimetry. Docking analysis was performed using autodock4 and LigandFit module of Discovery Studio 2.1.

Results: Griseofulvin strongly suppressed the dynamic instability of individual microtubules in live MCF-7 cells by reducing the rate and extent of the growing and shortening phases. At or near half-maximal proliferation inhibitory concentration, griseofulvin dampened the dynamicity of microtubules in MCF-7 cells without significantly disrupting the microtubule network. Griseofulvin-induced mitotic arrest was associated with several mitotic abnormalities like misaligned chromosomes, multipolar spindles, misegregated chromosomes resulting in cells containing fragmented nuclei. These fragmented nuclei were found to contain increased concentration of p53. Using both computational and experimental approaches, we provided evidence suggesting that griseofulvin binds to tubulin in two different sites; one site overlaps with the paclitaxel binding site while the second site is located at the αβ intra-dimer interface. In combination studies, griseofulvin and vinblastine were found to exert synergistic effects against MCF-7 cell proliferation.

Conclusions: The study provided evidence suggesting that griseofulvin shares its binding site in tubulin with paclitaxel and kinetically suppresses microtubule dynamics in a similar manner. The results revealed the antimitotic mechanism of action of griseofulvin and provided evidence suggesting that griseofulvin alone and/or in combination with vinblastine may have promising role in breast cancer chemotherapy.

Classical anti-mitotic drugs have failed to translate their preclinical efficacy into clinical response in human trials. Their clinical failure has challenged the notion that tumor cells divide frequently at rates comparable to those of cancer cells in vitro and in xenograft models. Given the preponderance of interphase cells in clinical tumors, we asked whether targeting amplified centrosomes, which cancer cells carefully preserve in a tightly clustered conformation throughout interphase, presents a superior chemotherapeutic strategy that sabotages interphase-specific cellular activities, such as migration. Herein we have utilized supercentrosomal N1E-115 murine neuroblastoma cells as a test-bed to study interphase centrosome declustering induced by putative declustering agents, such as Reduced-9-bromonoscapine (RedBr-Nos), Griseofulvin and PJ-34. We found tight ‘supercentrosomal’ clusters in the interphase and mitosis of ~80% of patients’ tumor cells with excess centrosomes. RedBr-Nos was the strongest declustering agent with a declustering index of 0.36 and completely dispersed interphase centrosome clusters in N1E-115 cells. Interphase centrosome declustering caused inhibition of neurite formation, impairment of cell polarization and Golgi organization, disrupted cellular protrusions and focal adhesion contacts—factors that are crucial prerequisites for directional migration. Thus our data illustrate an interphase-specific potential anti-migratory role of centrosome-declustering agents in addition to their previously acknowledged ability to induce spindle multipolarity and mitotic catastrophe. Centrosome-declustering agents counter centrosome clustering to inhibit directional cell migration in interphase cells and set up multipolar mitotic catastrophe, suggesting that disbanding the nuclear–centrosome–Golgi axis is a potential anti-metastasis strategy.

These findings suggest that griseofulvin inhibited growth of K562 cells and induced cell apoptosis through cell-cycle arrest and mitochondrial membrane potential decrease as well as caspase-3 and -9 activation. Further testing is needed to evaluate the potential of griseofulvin as a candidate in the chemotherapy of hematologic malignancies.

In this study, we demonstrate that apoptosis and G2/M cell cycle arrest were easily induced by treatment with the oral-antifungal agent, griseofulvin (GF). The mechanisms of GF-induced G2/M arrest were characterized as (a) induction of abnormal mitotic spindle formation, (b) elevation of cyclin B1/cdc2 kinase activity and (c) down-regulation of myt-1 protein expression. On the other hand, caspase 3 activation, Bcl-2 hyperphosphorylation and inhibition of the normal function of Bcl-2 associated with Bax were demonstrated to be the mechanisms of GF-induced apoptosis. DNA fragmentation and flow cytometry analyses demonstrated that combined treatment of GF with the cancer chemotherapeutic agent, nocodazole (ND), strongly potentiates the apoptotic effect and arrest of the G2/M cell cycle in 5 types of human cancer cells, but not in normal human keratinocytes (#76 KhGH). The combined treatment of GF and ND triggered the polymerization of purified tubulin in HT 29 but not in #76 KhGH cells. To further confirm these observations, the therapeutic efficacy was further examined in vivo by treating athymic mice bearing COLO 205 tumor xenografts, with GF (50 mg/kg), ND (5 mg/kg) or GF + ND. Combined treatment of GF and ND significantly enhanced the effect of ND, and led to cessation of tumor growth. These results suggest that chemotherapeutic agents (such as ND) administered in the presence of GF might provide a novel therapy for colorectal cancer.

The antifungal drug griseofulvin inhibits mitosis strongly in fungal cells and weakly in mammalian cells by affecting mitotic spindle microtubule (MT) function. Griseofulvin also blocks cell-cycle progression at G(2)/M and induces apoptosis in human tumor cell lines. Despite extensive study, the mechanism by which the drug inhibits mitosis in human cells remains unclear. Here, we analyzed the ability of griseofulvin to inhibit cell proliferation and mitosis and to affect MT polymerization and organization in HeLa cells together with its ability to affect MT polymerization and dynamic instability in vitro. Griseofulvin inhibited cell-cycle progression at prometaphase/anaphase of mitosis in parallel with its ability to inhibit cell proliferation. At its mitotic IC(50) of 20 muM, spindles in blocked cells displayed nearly normal quantities of MTs and MT organization similar to spindles blocked by more powerful MT-targeted drugs. Similar to previously published data, we found that very high concentrations of griseofulvin (>100 microM) were required to inhibit MT polymerization in vitro. However, much lower drug concentrations (1-20 microM) strongly suppressed the dynamic instability behavior of the MTs. We suggest that the primary mechanism by which griseofulvin inhibits mitosis in human cells is by suppressing spindle MT dynamics in a manner qualitatively similar to that of much more powerful antimitotic drugs, including the vinca alkaloids and the taxanes. In view of griseofulvin’s lack of significant toxicity in humans, we further suggest that it could be useful as an adjuvant in combination with more powerful drugs for the treatment of cancer.

Microtubules, composed of alphabeta tubulin dimers, are dynamic polymers of eukaryotic cells. They play important roles in various cellular functions including mitosis. Microtubules exhibit differential dynamic behaviors during different phases of the cell cycle. Inhibition of the microtubule assembly dynamics causes cell cycle arrest leading to apoptosis; thus, qualifying them as important drug targets for treating several diseases including cancer, neuronal, fungal, and parasitic diseases. Although several microtubule-targeted drugs are successfully being used in cancer chemotherapy, the development of resistance against these drugs and their inherent toxicities warrant the development of new agents with improved efficacy. Several antimicrotubule agents are currently being evaluated for their possible uses in cancer chemotherapy. Benomyl, griseofulvin, and sulfonamides have been used as antifungal and antibacterial drugs. Recent reports have shown that these drugs have potent antitumor potential. These agents are shown to inhibit proliferation of different types of tumor cells and induce apoptosis by targeting microtubule assembly dynamics. However, unlike vincas and taxanes, which inhibit cancer cell proliferation in nanomolar concentration range, these agents act in micromolar range and are considered to have limited toxicities. Here, we suggest that these drugs may have a significant use in cancer chemotherapy when used in combination with other anticancer drugs.

Griseofulvin, an antifungal drug, has been shown in recent years to have anti-proliferative activities. We report here the synthesis of new analogs ofgriseofulvin, substituted in 2′ by a sulfonyl group or in 3′ by a sulfinyl or sulfonyl group. These compounds exhibit good anti-proliferative activities against SCC114 cells, an oral squamous carcinoma cell line showing pronounced centrosome amplification, and unexpected cytotoxic activities on HCC1937 cells, a triple negative breast cancer cell line resistant to microtubule inhibitors.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Hi Emad! Great to hear that the markers are going down!!! This is a very good reason to celebrate! 🙂
As I see, the chemo administrated to your mother contains constantly microtubule dynamics inhibitors. This is how Griseofulvin and Mebendazole acts too. Next, I am curios to see what is the difference between the bindings sites for each of the microtubule dyn inhibitors (chemos or not).
What is the DCA dose and frequency of administration you are using?

about 6 months ago I tried this combination , chemo + DCA at the same time at the same day , I didn’t notice any difference , but I tried it just for 1 cycle only

Dr, Akbar Khan said that taking DCA with chemo at the same time may boost the effect or interfere as well

so his strategy is not to take chemo and DCA at the same time (the same day) , doing some tests will show if its good to take chemo + DCA together or not , here you can watch about his research in 2014 https://www.youtube.com/watch?v=9o12uT_d-Co

I don’t know if you see this video before , and I’m not sure if he is right about every thing he said

about Griseofulvin , it’s easy to get it just like Propanolol , but I need to check the liver enzymes to make sure that things are going good 🙂

Salinomycin , Escozul and the others are not easy to get , it will take some time , I hope it will be soon …

Thank for the info Emad. I will have a look at his research. Off course his view on best approaches with DCA is very important since he is the leader when it comes to treating cancer patients with DCA. But I need to understand why. 🙂

Welcome! There is no report to indicate interaction between the two, to my knowledge. Could you please report from time to time how is the Methylglyoxal treatment going for your mom? It would be great if you could add a comment on https://www.cancertreatmentsresearch.com/?p=1471 from time to time. Thank you in advance!

anyone knowing a reliable source for griseofluvin please let me know. the pagge above is not accepting normal payments, only bitcoin, i dont want to mess with it. on ebay etc there is no result. in my country a doctor needs to prescribe it…

If you can not get them, when I will be back home I will check those I have to see if the expiry date (although I have seen some report from the US Army indicating that unopened drugs may still have 80% effectiveness 20 years after the expiry date). If they are still good, I can send them to you as a donation.

Hello Daniel.
First of all, thank you for this site full of good advices. It is so helpful for my father who has stage 4 stomach cancer!

Today i would like to ask you if you have any idea which one is more efficient agains cancer : Mebendazol or Grisefuline? I saw that both have a similar effect, so do we have to choose to use just one of them?!
My father started taking Mebendazol this summer but it is difficult to get it in France. Mebendazol is not sold here. However, if Mebendazol is better or if it is dangerous to stop it and start Grisefuline, we will try to continue with it.
Thank you very much.

Thank you for your comment! I am happy to hear you find this website useful. At a high level the effect is similar but, Mebendazole has a different mechanism of action compared to Griseofulvin. So both could be used while addressing different mechanisms. If I would have to decide, I would continue with Mebendazole, and start using Pyrvinium Pamoate https://www.cancertreatmentsresearch.com/pyrvinium-pamoate/ as well first. Pyrvinium Pamoate has a great potential. The drawback is that it is not well absorbed but for cancers such as that of stomach where it can get in direct contact with the tumor there is a good chance to directly contact the tumor and work. If there is response I would continue with these, otherwise I would switch after several weeks to others such as Griseofulvin. Others from the same categ. of anti parasites with strong anti cancer potential are e.g. Ivermectin and Niclosamide. While using Griseofulvin check from time to time liver enzymes and if the liver is already in a difficult condition you need to be extra careful.

Mebenazole can also be ordered from eBay coming from e.g. Thailand or even from China as powder where is costs a few hundred euro for a kilo or so. To increase absorption, they should be taken with some fats, such as Omega3 oil.

I hope this answers your question and if here are others please let me know.

Daniel, thank you very much for your so fast and so detailed answer !!!
We will in this case continue Mebendazol, and try to find pyrvinium (it’s apparently stopped since 2011 in France, but I will try to order it in Germany).
My father has the lowest dose of Mebendazol- 200 mg per day. We will try to increase to double. For pyrvinium my father weighs 70kg, so he has to take 350mg = 7 tablets per day, that’s right ? Do you think it should be splited into several catches during the day ? I have seen that it’s more effective when the body is deprived of glucose. My father fasts for 3-4 days during chemotherapy (folfiri), so it might be a good idea to take pyrvinium during this week and take it every other week ? For the rest of the time he will continue Mebendazol. My father is already taking EPA / DHA, so it’s perfect. He takes itraconazole as you explained the week he is on chemotherapy, so we check his liver enzymes every two weeks.
Kind regards,
Dess

You are very welcome! Indeed pyrvinium is available in Germany, and other EU countries. 350mg would be max recommended daily dose according to the literature. The stools will be a bright red after that, due to pyrvinium. Yes, Dess taking every other week may be a good idea. Maybe switch every other week with Itraconazole not to add too much chemicals at the same time? Before chemo, it would help to exercise a bit if he can or drink some coffee to open up the blood vessels for chemo access. As often discussed, Paracetamol prior and during chemo could help the pro oxidant therapies like chemo. Other ideas to consider are discussed here https://www.cancertreatmentsresearch.com/if-chemotheraphy/ but probably you’ve seen this already.
A good idea, would be if in between the cycles of Chemo you could find a place where to do Salinomycin IV, but I am not sure if there is anyone in France doing that … I will check and let you know if I find something.

Thank you Daniel. We will start the next chemotherapy with coffee and paracetamol. As soon as I get to have pyrvinium it will start too to take it (maybe with a dose a little less than the maximum at least at the beginning). We did the RGCC test this summer and he seems pretty chemosensitive. What really worries me is that :
– Its tumor appears to have resisting populations – MDR1 overexpression = 60% and MRP = 40%.
– Growth factors are all overexpressed (vegf = 60%, fgf = 50%, pdgf = 45%, ang1 = 20%, ang2 = 25% …). So we’re trying to find ways to change that : he took Vascustatin and Quercetin for 2 months and soon he starts Angiostop and Liposomal Vitamin C. He takes a lot of other things too.

Happy New Year to you too, Daniel. I hope you know how much the information you give is useful. There are also many people who read you and use the information you give without necessarily being active. I’m sure that from above Mihaela is very proud of what you are doing, I was so sad about her loss, you would have deserved to win the battle…

Dear Dess,
I am very happy to hear good words about Daniel.
When people needs help,they are praying for help.But after taking help and the things goes wrong they begin to blame him.
I am sure that you understand the difference.
I am totally near him forever.
And we need people here like you.
We all hope you will share your future experience.
Happy new year.
Kind regards
Ergin

I really don’t know how to blame someone who gives all his knowledge and all his time to help people who are often absolutely unknown. Even doctors can’t promise to help the terminally ill, so if we don’t try something, what is remains ?

My father was diagnosed with stage 4 stomach cancer (many metastases in lymphoma) there are 22 months ago. The doctors gave him a few months to live. My sister and I have returned the world to try to save him. We didn’t know anything about cancer. His condition has had its ups and downs, but that is certain is that the Daniel’s site was one of my biggest discoveries.

So much information, so detailed, in the same place… Thanks to him we were able to use artemisia annua, Cimetidine, liposomal vitamin c, itraconazole, Mebendazol, etc.

Of course I can talk about our experience and knowledge (maybe much less than many of you here), if it can help someone… I can’t speak myself easily in English, I use Google translation and my husband checks my text, for fear saying things very incomprehensible…

Hi Dess,
I wrote this message that night .Everyone was celebrating the new year but i was not.I was in a too emotional mode.Forgive me pls,in special days when i drink stg i should not write in this website.

There is no problem with your message. I’m deeply sorry for the loss of your mom. You did everything you could. I think we can help, and if we are lucky we can extend the lives, but there is always a part of things that depends of God only. I believe that you will be together again one day. Your contribution here is very useful, and I imagine how is difficult for you to continue to speak about this disease. 🙁 Take care !

Hi Dess,
Imagine a child who dont let his mother to go to toilet.Iwas just sticked to her from 0 year.
I left my job 2 years ago and began to search for an effective treatment.Believe me if you see my mail,you ll see 100s of scientist and doctors mail.I shared some of them in this website.
I really tried and learn by the help of Daniel and teach to people lots of treatments.From nerium oleander to 3BP,salinomycin,oleuropein ,nano silver,tarantula cubensis and more and more.
We saw here combos like DCA+HCA+CA plus plus…..This website is special because of Daniel.He gave me lots of his time by phone,skype ,mail,whatssup and messages here.
1-2 weeks ago i got a phone call from a patients son.He called me to use phlorizin and says you are the only one who knows how to use it.Can you imagine???Responsibility???
Again i entered the cancer world.
Today i learned that our friend Jandros brother passed away.I throw my phone to wall.
My physcology is not good enough to enter cancer world again.But people need help.
Thank you for your understanding.
Kind Regards
Ergin

Thank you very much for your kind words and I am very glad to hear that with your research you are already helping your dad to live longer. This is a proof of the fact that there is much more that can be done for the people in need.

Very nice to read in your other comment the way you translate the msgs with Google translator and help of your husband 🙂 It’s great to see how technology brings us closer to each other regardless of our origin and language.

Hello Daniel, I take a little time to answer, sorry. My father was hospitalized for a pulmonary embolism. Three months ago he had a thrombosis, he was under LMWH injections for a month and suddenly there was this embolism. I searched a lot and the doctor confirmed it : it comes from cancer. And I think itsn’t a very good sign. He is again under LMWH injections and it will last a while I think.

Regarding your last message, I looked for MDR inhibitors you speak. Tetrandrine looks interesting. Do you know which dose to take and from which company we may have it (Nutrayours maybe ?). I will check the price. I saw that Verapamil has a similar effect, though may be less strong. What do you think about it ? I think I can find Verapamil easily and it’s especially really cheap. Unfortunately with all the cares, we are obliged to look also the financial aspect. On the other hand I read that Verapamil interacts with Cimetidine. I really care about Cimetidine and I don’t want to stop it, but is it safe to take both at the same time ? Itraconazole also interacts with Verapamil, my father doesn’t take it every day, but if we stop Verapamil while taking Itraconazole this may not be effective ? I don’t know what to do. Lovastatin also interacts with Itraconazole… We want to use several things, but with all the drugs that my father takes I’m afraid to make an interaction mistake…

I’m going to buy Piperine. In one of the articles you say that the usual recommended dose is 5-15 mg / day but for anticancer effect we must go beyond that. Do you know how much mg / day we can use safely go ?

I find the article on TM very interesting. I’m going to see with laboratories if we can take blood tests without prescription, because I know in advance that his doctor will not want (he is very reluctant to anything that is not official).

Can you tell me how to take paracetamol during chemotherapy? What dose and for how many days?

My father took Quercetin and I thought it had a positive effect on him. He took it with Bromelain. RGCC has advised us to try different solutions to avoid resistance. So we will stop it and it will be reintroduced later.